This month marks the 80th anniversary of doctors injecting radioactivity into their patients – not as part of evil experiments, but to help to diagnose and treat disease. And in spite of being only 80 years old, the field of nuclear medicine has become impressively versatile and valuable over the decades, giving physicians the ability to, in effect, “see” within their patients’ bodies to learn what was ailing them. Here’s how it works.
Tracking tagged molecules
Every organ, every tissue in our bodies has a different biochemistry and uses different molecules and elements. The thyroid, for example, uses iodine to function and to produce the hormones that help to regulate our metabolism; the brain thrives on an exclusive diet of glucose; our bones incorporate calcium, phosphorus, and a handful of other elements. So if we want to learn about how the thyroid is functioning – or to learn where in the body metastatic thyroid tissue has migrated – injecting radioactive iodine will cause the thyroid tissue to become radioactive, making it easy to find. Similarly, adding radioactive atoms to glucose molecules can help us to see what’s going on in a patient’s brain while adding radioactivity to molecules that are used by growing bone can tell a physician where there is a small fracture that has begun to knit together.
Physicians have know for decades that certain organs and different tissues have different biochemical characteristics. But until the middle of the last century this knowledge, while interesting and important, was of no help whatsoever in diagnosing illness – but with the advent of nuclear technology (specifically, nuclear reactors and accelerators) this began to change. Radioactive atoms emit radiation (of course!) and that includes gamma rays that can penetrate through the overlying tissues to be detected from outside the body.
So say a patient has metastatic thyroid cancer – when I-131 is injected into the patient the iodine will seek out thyroid tissue, including any metastases where cancerous thyroid cells have spread through the body; when the patient is scanned with a gamma camera (more on this shortly) these clumps of now-radioactive thyroid tissue will show up as bright spots on the scan. Give the patient a higher dose and, instead of revealing their locations, the radioactive iodine will deliver a high enough dose of radiation to destroy the cancerous tissue.
In 1934, Frederick and Irene Joliet Curie formed radioactive P-30 by bombarding stable aluminum with alpha particles. Not long after, Enrico Fermi, speculating that neutrons’ lack of an electrical charge might make them even more effective, began slamming neutrons into as many elements as he could get his hands on to see what would happen. Four years later Fermi was awarded the Nobel Prize for this work.
The Second World War slowed non-war-related research; at the same time, it provided wonderful new tools for producing artificial radionuclides – nuclear reactors and particle accelerators – as well as new instruments with which to measure and characterize the radiation they gave off. After the war, the stage was set for putting these to use in medicine.
While there had been some early work with nuclear medicine in the 1930s, the first bona fide treatment came about in 1946 with the use of I-131 to stop the growth of a thyroid tumor and the subsequent realization that lower doses could be used for imaging rather than destroying the diseased tissue. Over the ensuing years and decades, nuclear medicine physicians learned to insert radioactive atoms into molecules that would be taken up by other organs, by cancerous tumors, by healing bone, and more – the current list of nuclear medicine procedures published by the Nuclear Medicine Technologist Certification Board lists 78 procedures using radiopharmaceuticals not even dreamed of in 1946 (https://www.nmtcb.org/exam/procedureslist.php). And the most recent additions – positron-emitting radionuclides (often used in conjunction with CT scanners) – make use of a particle of antimatter, most commonly encountered in science fiction.
It’s possible to find out where the radioactivity is collecting without creating an image at all. If I give someone I-131, for example, I can start scanning their body with my Geiger counter – as I survey I’ll notice I get a low count rate at their feet, higher when surveying their pelvis and abdomen, and highest when my detector is over their throat. This would tell me that there’s not much in the feet or legs that absorbs iodine, that it collects in the bladder and colon while waiting for the person to urinate or defecate, and that the thyroid collects iodine more effectively than any other part of the body. On the other hand, if I got a high count rate from, say, the underarm, groin, or liver then I might suspect a metastatic tumor that had spread to lymph nodes or to the liver.
The thing is, while many scientists and engineers are comfortable with numbers, they’re a little unusual in that; most people can get more information from a picture than from a table of numbers. Finding a way to produce images of where the radioactivity was collecting was a way to make this technique accessible to a much wider range of physicians
The Moritz Orthodiagraph – devised by Friedrich Moritz, of Munich (1861-1938)
The problem is that gamma rays are given off in all directions – so if I’m holding my radiation detector over, say, an I-131 patient’s nose, it’s going to show a high count rate. This isn’t because some iodine ended up in the person’s nose – it’s because the iodine in the patient’s thyroid will emit gamma radiation in all directions, including into my radiation detector. Unless I can find a way to screen out all of the gammas except for those that are directly beneath my detector.
One way to do this is to take a piece of lead and drill an array of holes through it, putting an array of radiation detectors on the other side of the lead. If a particular detector registers a “hit” then I can be sure that the gamma was emitted directly beneath that hole in the lead. Doing this with the entire array of holes and detectors gives us an image of the part of the body beneath the array; scanning the array over a part (or all) of the body can tell us where the radionuclide has collected. The former (parking the array over, say, the neck) can help us to locate small nodules within the thyroid while the latter (assembling an image of the entire body) can show us where metastatic thyroid tissue has landed.
One of the problems with nuclear medicine is that it shows where the radionuclide ends up, but not necessarily what structures it ends up in. For example, a “hot spot” in the abdomen might be the result of radioactivity in the liver, the gall bladder, one of the ducts between the liver, gall bladder, and digestive tract, the connective tissue in the area, or maybe even in the muscles that line the abdominal cavity. Taking “pictures” from different angles can help to narrow down the possible location – a hot spot halfway between the front and back walls of the abdomen, for example, is more likely to be in the liver than in the abdominal muscles. But even the best gamma camera still has limits to their ability to precisely resolve the location – precise information requires a higher-resolution image; we can get that sort of precise three-dimensional imaging from a CT scan. Thus, the PET-CT – a device that can be used to show not only metabolic or biochemical activity (where the radiopharmaceutical collects) but also the structures in which the hot spots lie.
Images from a Ga-68 PSMA PET-CT in a man with prostate cancer shows tumors in lymph nodes in the chest and abdomen. Credit: Adapted from Int J Mol Sci. July 2013. doi: 10.3390/ijms140713842. CC BY 3.0.
Injecting a patient with radioactivity raises some safety concerns – for the patient, for the medical staff, for their family, and for others with whom they might come in contact.
Consider the I-131 patient we discussed earlier. I-131 gives off both beta and gamma radiation; the beta radiation is not much of a concern because it’s trapped within the body, but gamma rays can (and do) expose others. The key is to limit that exposure.
When a patient is in the hospital, workers can use the principles of Time, Distance, and Shielding to reduce their exposure and that of others. Reducing the amount of time anyone is near a patient reduces their exposure, as does increasing the distance to the patient. Nurses, for example, can stand at the foot of the bed instead of at the head to be further from the thyroid; if they must be at the head of the bed, they can stand back a step instead of standing at the bedside. Simply taking one step away from the patient can reduce radiation exposure by a factor of four or greater. In addition to this, many hospitals install lead shielding in the walls surrounding the rooms where their I-131 patients remain during their stay; this reduces radiation exposure to those in adjacent rooms.
Radiation safety for the patient primarily takes the form of carefully calculating the amount of I-131 that’s administered – a high enough dose to obtain a good image or to ablate the thyroid tissue, but not much more than that to avoid excessive radiation exposure to healthy tissues. In addition, nuclear medicine patients are usually given instructions on how to reduce radiation exposure to their family and friends when they return home.
These instructions usually include cautions to use a separate bathroom than other family members (if possible), not to share cups or cutlery with others, not to hold babies and young children on their lap, to sleep in a separate bed from spouse and children, and so forth – the idea is to not only reduce radiation exposure from the gamma radiation emitted from their bodies but also to reduce the chance for family members to come in contact with radioactive contamination. In cities with widely used mass transportation (or patients who rely on mass transit) there is also a common admonition to try not to sit or stand too close to other passengers if possible. These precautions might last for only a few hours (with most PET radionuclides), for a few days (in the case of Tc-99m), or for a few weeks (in the case of I-131).
One other consideration in recent years is that many cities have established networks of radiation detectors as part of their counterterrorism efforts, and nuclear medicine patients cause the majority of radiation alarms that come in. In the decade or so that I’ve worked with law enforcement on radiological interdiction, I’ve seen far more alarms from nuclear medicine patients than from all other sources combined. For this reason, many nuclear medicine physicians will give notes or cards to their patients so that, if they do trigger a radiation alarm, they can show the cards to the police.
After 80 years nuclear medicine is a mature methodology with a solid technological and scientific foundation. Over the years it’s been developed to a high level, and in recent years there have been about 15 million procedures annually – both diagnostic and therapeutic. For what it’s worth, I account for some of those procedures – I’ve had a number of scans over the last decade or so, so I can personally confirm that it doesn’t hurt, it doesn’t make one dangerously radioactive, and it doesn’t put others at risk. And the information that it provides can either be used to help guide treatment – or to put one’s mind at ease. Either way, it’s useful to both patients and physicians – probably one of the reasons it’s still in use.